Nucleic acid-targeting proteins and enzymes are essential to various aspects of genetic information processing, such as replication, transcription, splicing, translation, recombination, DNA/RNA degradation, gene amplification/deletion/rearrangement, DNA repair, transposition, retroviral integration, and gene inactivation/silencing. The detection of size changes in nucleic acids is the key to diverse research areas such as nucleic acid-protein interaction mapping, nuclease inhibitor drug screening, and development of oligonucleotide-based therapeutics. The detection schemes usually require the synthesis of multiple special oligonucleotide substrates, and the labeling of the oligonucleotide(s) with fluorescent, electrochemical or radioactive probes (see, e.g., Behrens et al. (2004) Syst. Appl. Microbiol., 27: 565-572; Smith and Anslyn (1994) Anal. Biochem., 220: 53-57; Hillier et al. (2004) Bioelectrochemistry 63: 307-310), especially for nuclease-based methods. There remains the challenge of detection within small volumes and in real time, a problem made more pronounced with the advent of microarray and microanalytical devices, and the accompanying unprecedented reduction in assay volumes down to the nanoliter or even picoliter range.
As one of the promising technology platforms for measuring small changes, surface plasmon resonance (SPR) spectroscopy is an ultrasensitive optical method that measures the refractive index or dielectric constant of liquids or media in contact with the surface of metallic thin films. Conventional bulk-scale surface plasmon resonance sensors have been demonstrated to measure properties such as: the thickness of insulators, the refractive index of thin dielectrics, the detection of small molecules, analyte concentration, protein-protein/antibody-antigen interaction and dissociation kinetics, DNA hybridization, and mixture proportions.